Beyond Neuroimmune Communication: Messengers and Cellular Targets
Carmen Guaza, Instituto Cajal CSIC
Details
The interest in the functional interactions between the Nervous System and the Immune System, without overlooking the Neuroendocrine System, has shaped my scientific career from an integrative perspective in both physiological and pathological processes. Immune messengers, such as cytokines and chemokines are not only mediators of neuroinflammation but also essential for the protection and repair of the CNS. In multiple sclerosis (MS), the pathology on which we have focused through animal models, cell models and in MS itself we have identified new therapeutic targets in an effort to slow its progression. We found that the endogenous cannabinoid system plays a protective role in brain-immune cross-communication, targeting brain endothelial cells, microglia, astrocytes, oligodendrocytes, and their progenitors. The ability of microglia to acquire various activation states, -crucial for maintaining homeostasis, inflammation, and repair- is modulated by endocannabinoid signaling (eCBSS). This signaling system i) restores the inhibitory immune checkpoint CD200-CD200R which is key in neuron-microglia interaction and is disrupted at certain stages of MS ii) enhances the removal of myelin debris by microglía, thereby promoting the differentiation of oligodendrocyte progenitors cells (OPCs) and leading to remyelination in a viral model of MS iii) reduces proteoglycan accumulation and astrogliosis around plaques, facilitating remyelination and functional recovery in mice. In recent years, we have also become interested in the gut-brain axis and the characterization of the microbial profile in MS models.
Tripartite Synapses: Astrocyte regulation of synaptic function, network activity and animal behavior
Alfonso Araque
Oligodendrocytes in brain energy metabolism and Alzheimer’s disease
Klaus-Armin Nave
Details
We found that oligodendrocytes, best known for making myelin and allowing fast saltatory impulse propagation in the CNS, also provide glycolysis products as metabolic support for fast spiking axons. Moreover, in white matter tracts, the myelin sheath is a dynamic compartment that continuously turns over. Thus, when glucose is limiting, myelinating oligodendrocytes can rapidly metabolize myelin-derived fatty acids to meet their own energy needs for survival and to prevent irreversible axon degeneration. Interestingly, oligodendrocytes and neurons both express and process the amyloid precursor protein (APP), but A peptides that are generated within oligodendrocytes contribute largely to the cortical and not the white matter plaque load in Alzheimer’s disease (AD) mouse models. This raises the question how oligodendroglial A is reaching neuronal plaques. In the aging brain, there is a gradual decline of myelin structural integrity, which is likely to affect myelin turnover and the metabolic coupling between oligodendrocytes and axons. This could be a risk factor for the onset of AD, because myelin dysfunction acts as a driver of amyloid plaque deposition in mice. This is in part due to the inhibition of microglia in phagocytosing A, which also identifies a new therapeutic target for delaying the onset of AD.
The regulation of neural stem cell quiescence by a physical niche
Isabel Fariñas. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Departamento de Biología Celular, Biología Funcional y Antropología Física, Instituto de Biotecnología y Biomedicina (BioTecMed), Universidad de Valencia
Details
New neurons for highly plastic olfactory circuits are produced in the subependymal zone (SEZ) of the adult mammalian brain. Neural stem cells (NSCs) in this niche have access to a wide range of regulatory signals that promote continuous lifelong neurogenesis while preserving the stem cell pool. NSCs derive from radial glial cells, which are the primary embryonic progenitor type in the vertebrate brain, and inherit from them part of their transcriptional program, a bipolar elongated morphology with apico-basal polarity that allows for unique interactions with neighboring cell types, and markers associated with the astrocytic lineage. In contrast to their fetal counterparts, most adult NSCs remain in a quiescent state under physiological conditions. It is now widely accepted that NSCs in the SEZ exist in at least three states: quiescent (q), quiescent but prone to activation or primed (p), and activated (a), each characterized by unique and distinct transcriptional profiles. Transitions between states likely involve significant changes in cellular physiology tightly regulated by both intrinsic and extrinsic factors. We have found that entry into quiescence is associated with the deposition of specific extracellular matrix components and that adhesion to the matrix produced in response to pro-quiescent signals alone can induced a quiescent-like state in proliferative NSCs. This entry into quiescence depends on the RhoA-associated kinase ROCK and yes-associated protein (YAP) transcriptional activity. YAP/TAZ deletion in NSCs leads to the loss of ECM deposition and quiescence in vivo suggesting that they regulate the physical niche and a quiescence-associated gene expression program in response to mechanical cues.
Organizers
Gertrudis Perea; Instituto Cajal, CSIC, Madrid, Spain
Speakers
Astrocyte Kir4.1 expression level territorially controls excitatory transmission
Dmitri Rusakov. UCL Queen Square Institute of Neurology, University College London, UK
Astrocytes in higher brain function
Inbal Goshen. The Edmond & Lily Safre Center for Brain Sciences, Jerusalem, Israel
ControControl of dendritic computation by astrocytic D-serine and glycine signallingl
Christian Henneberger. University of Bonn, Bonn, Germany
Astrocyte tuning of social behaviors
Gertrudis Perea. Instituto Cajal, CSIC, Madrid, Spain
Details
The symposium addresses the pivotal role of astrocytes play alongside neurons in shaping brain activity and complex behaviors. Astrocyte-neuron signaling represents a cutting-edge frontier in neuroscience, offering new insights into brain function that extend beyond traditional neuron-focused research. Astrocytes, a type of glial cell once considered merely supportive, are now recognized as active participants in the brain’s signaling processes. They modulate synaptic transmission, regulate blood flow, and play critical roles in neurovascular coupling and metabolic support to neurons. This symposium highlights cutting-edge discoveries by experts in the field revealing how astrocytes contribute also to higher brain functions, such as memory formation, learning, and emotional processing. Therefore, astrocyte-neuron «crosstalk» results essential for understanding the brain as an integrated system rather than as isolated parts.
Organizers
Manuel Valero. Hospital del Mar Research Institute, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain
Speakers
Inhibitory circuits supporting developmental network dynamics
Laura Modol. Hospital del Mar Research Institute, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain
Cooperative action of interneuron classes supports the hippocampal function
Manuel Valero, Hospital del Mar Research Institute, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain
Role of interneurons in hippocampal network dynamics for learning and memory
Antonio Fernández-Ruiz, Department of Neurobiology and Behavior. Cornell University, Ithaca (NY), US.
Avalanche dynamics and interneurons in the hippocampus during sleep following spatial learning
Jozsef Csicsvari, Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.
Details
Interneurons constitute a minority (15%) of cortical neurons but embody much of the neuronal genetic diversity. What evolutionary advantage might have driven this disproportionate diversity of interneurons? While the scientific community agrees that this diversity is essential for brain function, our ability to dissect their functional roles has been limited until recent years. In this symposium, we bring together four speakers from diverse disciplines, ranging from development to learning and memory, who exemplify the complexity and significance of integrating interneuronal diversity into the investigation of the neural mechanisms of behavior.
Organizers
Ana Uzquiano, Harvard University, Cambridge MA (USA)
Sara Bizzotto, Imagine Institute, Inserm, Paris (France)
Speakers
Profiling and programming human in vitro neuronal diversity at single-cell resolution
Hsiu-Chuan Lin. Centre for Genomic Regulation (CRG), Barcelona (Spain)
Unlocking human cortical development through brain organoids
Ana Uzquiano. Harvard University, Cambridge MA (USA)
Identifying the first emergence of cortical disorder risks
Gabriel Sanpere. Hospital del Mar Research Institute, Barcelona (Spain)
Somatic mosaicism and cell lineages in human neurodevelopment and disease
Sara Bizzotto. Imagine Institute, Inserm, Paris (France)
Details
In this symposium, we bring together complementary expertise in the neurodevelopment field to tackle specific questions about how the human brain is built, with a focus on cell fate in development, evolution and disease.
Organizers
Arnaldo Parra-Damas, Universitat Autònoma de Barcelona
Carlos Saura; Universitat Autònoma de Barcelona
Speakers
Impact of Aβ and tau pathologies on the transcriptomes of excitatory and inhibitory hippocampal neurons
Arnaldo Parra-Damas. Universitat Autònoma de Barcelona.
The role of hippocampal inhibition in memory deficits and functional recovery in Alzheimer’s disease mice
Laure Verret. Université de Toulouse, Research Center on Animal Cognition, CNRS, Toulouse, France.
Interneuron hyperexcitability is an early driver of hippocampal network imbalance in AD mice
Ronald E. Van Kesteren. Vrije Universiteit Amsterdam, Netherlands
Gene regulatory network alterations in Alzheimer’s disease at single-cell resolution
Mireya Plass. Universitat de Barcelona & IDIBELL.
Details
Recent advances on cell-specific/single-cell profiling and modulation technologies have allowed detailed characterization of specific neural populations during physiological and pathological conditions. In neurodegenerative diseases, early altered activity of brain circuits is associated with transcriptional and pathophysiological changes affecting specific cell types and their interactions, including excitatory and inhibitory neurons. In Alzheimer’s disease (AD), excitatory neurons are the main degenerating population, although emerging evidence indicate that early dysfunction of GABAergic interneurons mediate excitatory/inhibitory (E/I) imbalance, leading to hyperexcitability and memory loss. In this symposium, we will present recent findings on the cellular and molecular mechanisms mediating E/I dysfunction of neural circuits in neurodegenerative diseases, including AD.
Organizers
José Vicente Torres Pérez. Department of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, Spain
Speakers
Impact of cerebral asymmetry on quantitative abilities in zebrafish
Maria Elena Miletto-Petrazzini, Department of Biomedical Sciences, University of Padova, Italy
Exploring number sense deficit in Williams syndrome using zebrafish
José Vicente Torres Pérez, Department of Cellular Biology, Functional Biology and Physical Anthropology, University of Valencia, Spain
Genetic variance in numerosity and its association with working memory
Caroline H Brennan, School of Biological and Behavioural Sciences, Queen Mary University of London, United Kingdom
Single neuron coding of numerosity in chicks and zebrafish developmental insights
Mirko Zanon, Centre for Mind/Brain Sciences, University of Trento, Italy; and Translational Imaging Center, Michelson Center for Convergent Bioscience, University of Southern California, Los Angeles, USA
Details
This symposium delves into a rapidly advancing area of cognitive neuroscience that remains underexplored: Numerical cognition or «Number sense», which refers to the innate ability to perceive and estimate quantities. This fundamental cognitive skill relies on an evolutionary conserved mechanism in all vertebrates. This symposium will uniquely combine insights from genetics, neurobiology, and comparative psychology to uncover the biological underpinnings of this vital cognitive process.
